D Calvin

D Raz-Prag

D Vozzi

DI Scheffer

E Kubo

H Azaiez

HG Sutherland

I Del Castillo

J Shen

JM Schwarz

JT Robinson

K Wang

KJ Livak

KS Pollard

LNF Darville

LT Chylack

M-C Shun

MS Hildebrand

N Hilgert

O Isken

P Danecek

P Gasparini

P Kumar

PA Frischmeyer

PD Stenson

T Elkan-Miller

X Chen

X Estivill

X Liu

Z Ge

Scientific Reports

AbstractHereditary Hearing Loss (HHL) is an extremely heterogeneous disorder. Approximately 30 out of 80 known HHL genes are associated with autosomal dominant forms. Here, we identified PSIP1/LEDGF (isoform p75) as a novel strong candidate gene involved in dominant HHL. Using exome sequencing we found a frameshift deletion (c.1554_1555del leading to p.E518Dfs*2) in an Italian pedigree affected by sensorineural mild-to-moderate HHL but also showing a variable eye phenotype (i.e. uveitis, optic neuropathy). This deletion led to a premature stop codon (p.T519X) with truncation of the last 12 amino acids. PSIP1 was recently described as a transcriptional co-activator regulated by miR-135b in vestibular hair cells of the mouse inner ear as well as a possible protector against photoreceptor degeneration. Here, we demonstrate that it is ubiquitously expressed in the mouse inner ear. The PSIP1 mutation is associated with a peculiar audiometric slope toward the high frequencies. These findings indicate that PSIP1 likely plays an important role in HHL.</jats:p

Giorgia Girotto

Déborah I. Scheffer

Anna Morgan

Diego Vozzi

Elisa Rubinato

Mariateresa Di Stazio

Enrico Muzzi

Stefano Pensiero

Anne B. Giersch

David P. Corey

Paolo Gasparini

Crossref

PSIP1/LEDGF: a new gene likely involved in sensorineural progressive hearing loss

PSIP1/LEDGF: a new gene likely involved in sensorineural progressive hearing loss

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